title: Activation-induced cytidine deaminase auto-activates and triggers aberrant gene expression.
abstract: DNA methylation is a well-characterized epigenetic landmark involved in transcriptional regulation; however, mechanisms underlying its regulation remain poorly characterized. Recent studies demonstrate that activation-induced cytidine deaminase (AID) is involved in active DNA demethylation. AID is aberrantly expressed in inflammation-associated cancers and generates point mutations; however, cellular disorders attributed to its demethylation function are largely unexplored. Here we demonstrate that ectopic AID expression perturbs tumor-related gene expression. AID (with Gadd45) activated a methylated paired box gene 5 (Pax5) reporter construct, and induced expression and association of endogenous Pax5 with the AID promoter, suggesting that aberrant AID expression triggers an auto-activation circuit to consolidate self-expression.
authors.affiliation: Immuno-Medical Science, Division of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Isobe
authors.forename: Soken-Nakazawa J
authors.initials: SN
authors.lastname: Song
authors.forename: Prabha
authors.initials: P
authors.lastname: Tiwari
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ito
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yoshizaki
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D018899:CpG Islands; D003564:Cytidine Deaminase / Q000378:metabolism*; D019175:DNA Methylation; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000378:metabolism; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D003564:Cytidine Deaminase; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; D000098830:AICDA (Activation-Induced Cytidine Deaminase); C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C497281:PAX5 protein, human
keywords: 5-aza-2′-deoxycytidine; 5-aza-dC; AID; COBRA; ChIP; Demethylation; Gadd45; H-Ras; HSV-TK; Harvey rat sarcoma viral oncogene homolog; NF-κB; PGCs; Pax5; RT-PCR; SV40; TNFα; TSS; chromatin immunoprecipitation; combined bisulfite restriction analysis; growth arrest and DNA damage inducible protein 45; herpes simplex virus-thymidine kinase; nuclear factor-κB; paired box gene 5; primordial germ cells; qRT-PCR; quantitative RT-PCR; reverse transcription-polymerase chain reaction; simian vacuolating virus 40; transcription start site; tumor necrosis factor α